Comparison of chlordecone and estradiol effects on splenic T-cells in (NZBxNZW)F(1) mice.
Previous studies have shown that treatment of ovariectomized females with 17-beta estradiol (E2) accelerates the development of autoimmunity in the (NZBxNZW)F(1) murine lupus model. Treatment with estrogenic organochlorine pesticides (OCPs) such as chlordecone produces a similar effect. Although it is reasonable to postulate that the effects of chlordecone and related OCPs on autoimmunity are due to their estrogenic effects, this has not been clearly demonstrated. The objective of this study was to compare effects of chlordecone and E2 on splenic T lymphocyte parameters plausibly related to autoimmunity; specifically, on T-cell phenotype and functions. Ovariectomized (NZBxNZW)F(1) mice were treated for 6 weeks with implanted sustained-release pellets containing chlordecone or E2 at dosing rates shown previously to significantly shorten time to onset of disease. E2, but not chlordecone, increased the percentage of activated and memory CD4 T-cells, and reduced naive CD4 T-cells. E2 also elevated CD25 and glucocorticoid-induced TNF receptor (GITR) levels in CD4 T-cells, an effect not shared by chlordecone. On the other hand, both chlordecone and E2 increased Bcl-2 expression in CD4 T-cells and reduced CD4 T-cell apoptosis without affecting their proliferation. Although both treatments increased TNF-alpha and IL-2 secretion by CD4 T-cells, only chlordecone increased secretion of IFN-gamma and GM-CSF. E2, but not chlordecone, increased IL-10 secretion. These observations indicate that although it is considered an estrogenic OCP, chlordecone exerts effects on splenic T-cells that are different in a number of ways from E2.
Wang
Fei
F
Department of Pharmacology and Therapeutics, J. Hillis Miller Health Science Center, University of Florida, Gainesville, FL 32610, USA.
Sobel
Eric S
ES
Butfiloski
Edward J
EJ
Roberts
Stephen M
SM
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D015704:CD4 Antigens / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D007631:Chlordecone / Q000633:toxicity*; D004958:Estradiol / Q000633:toxicity*; D004967:Estrogens / Q000633:toxicity; D005260:Female; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D051379:Mice; D008814:Mice, Inbred NZB; D008815:Mice, Inbred Strains; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D010575:Pesticides / Q000633:toxicity; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015704:CD4 Antigens; D004967:Estrogens; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D010575:Pesticides; D019253:Proto-Oncogene Proteins c-bcl-2; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D004958:Estradiol; D007371:Interferon-gamma; D007631:Chlordecone